Regioselective and Enantioselective Synthesis of β‐Indolyl Cyclopentenamides by Chiral Anion Catalysis

The regioselective and enantioselective synthesis of β‐indolyl cyclopentenamides, a versatile chiral building block, by asymmetric addition of indoles to α,β‐unsaturated iminium intermediates has been achieved through chiral anion catalysis. Key to the success of this methodology is the generation of a chiral anion‐paired ketone‐type α,β‐unsaturated iminium intermediate from α‐hydroxy enamides. Preliminary mechanistic studies and DFT calculations are consistent with a mechanism involving multiple, concurrent pathways for isomerization of the initially formed azaallylcation into the key α,β‐unsaturated iminium intermediate, all mediated by the phosphoric acid catalyst. Step by step: The regio‐ and enantioselective synthesis of β‐indolyl cyclopentenamides was achieved by asymmetric addition of indoles to α‐hydroxy enamides through chiral anion catalysis. Key to this transformation is the generation of a chiral anion‐paired ketone‐type α,β‐unsaturated iminium intermediate through an unexpected isomerization of the initially formed azaallylcation intermediate. CPA=chiral phosphoric acid.